Bordetella pertussis is the etiology of whooping cough which remains a significant cause of morbidity, particularly in young children. Despite successful childhood vaccination programs, outbreaks still occur in schools, medical institutions, and in communities both nationally and worldwide. This disease is underdiagnosed and grossly underreported, but the CDC records approximately 6,000 to 8,000 cases of pertussis each year with the highest incidence of disease in young children, the age group in whom disease is most severe. Several studies suggest that adolescents and adults are the reservoir of infection and source of transmission to young infants. Since B. pertussis is a pathogen only to humans, interrupting infection and transmission between individuals by improved vaccination and treatment may improve disease control lead to disease eradication. The goal of this proposal is to develop a safe human challenge model for detailed study of B. pertussis infection in healthy adults to elucidate the important pathogenic, clinical, epidemiological and immunologic aspects of B. pertussis infection. To date, most of our understanding of B. pertussis pathogenesis have relied on animal models, which are inadequate for application to human disease. With a human model, we will be able to 1) study the pathogenesis of B. pertussis in humans and evaluate the initial host inflammatory and immune responses following challenge, 2) evaluate susceptibility, incubation period and early clinical manifestations of B. pertussis, 3) characterize and expand our understanding of immunologic determinants of susceptibility and protection, 4) define mechanisms for long- term immunity to B. pertussis and 4) evaluate vaccine efficacy for the prevention of B. pertussis infection. Such information has not and probably cannot be derived from laboratory animals or other clinical trials and are crucially important to devise immunization strategies for improved pertussis control. Human challenge models are invaluable in the study of enteric infections, malaria, influenza and other respiratory infections. These models have proven useful to study the sequence of infection and disease, vaccine efficacy, antibiotic efficacy, and immune mechanisms involved with disease pathogenesis and protection. We hope to greatly refine the understanding of B. pertussis and develop improved means for diagnosis and prevention of disease in all age groups.